The proposed research will employ synthetic polymers of amino acids (random and known sequences) to study parameters of the immune responses such as the nature of antigenic determinants, mechanism of antigen-antibody interactions, genetic control of the immune responses. Antigenic determinants will be isolated (or synthesized) from enzyme digests of polymers. The minimum size of the determinants will be obtained from inhibition studies. The minimum size of the oligopeptide that can elicit cellular vs humoral immune responses will be studied in guinea pigs and mice. Polymers related to the mucopeptide structure of Strep and Staph and the encephalitogenic protein will be synthesized and studied for immunogenicity and ability to elicit a protective response in rabbits and guinea pigs. Attempts will be made to obtain homogeneous antibody for study of the nature of, and the amino acids in the combining site. Affinity labelling procedures will be applied to sheep and rabbit immunoglobulins. Tritium exchange techniques and spectral absorption methods will be employed to measure the nature of conformational changes that antibodies and antigens undergo upon interaction. Attempts will be made to correlate the changes observed with such phenomena as complement fixation, and differences in responsiveness against polymers of lymphocytes (T cells and B cells) from "responder" and "non responder" mice, i.e. the nature of changes induced in cells upon interaction of antigen with the appropriate receptor site. Genetic control of the immune response (IR) and the role of IR genes will be studied in inbred mice, guinea pigs and rats. We will attempt to elucidate problems such as: the possible mechanisms of action of lR genes, the cell type (T cell vs B cell) in which genes are expressed, the relationship (mapping) of IR genes to histocompatibility loci as determined with known "crossover" recombinant mice, the nature of the gene product (receptor site) in responder vs non responder animals, the nature of "tolerance" in the non responder animal.